SS-31 (Elamipretide)

Overview

SS-31 (elamipretide, Bendavia, MTP-131) is a mitochondria-targeted tetrapeptide that concentrates in the inner mitochondrial membrane. Developed by Stealth BioTherapeutics, it has undergone Phase II and III clinical trials for Barth syndrome, primary mitochondrial myopathy, and heart failure. In September 2025, FDA granted it accelerated approval (as Forzinity) to improve muscle strength in patients with Barth syndrome weighing at least 30 kg, the first approved therapy for the condition.

Mechanism of Action

SS-31 selectively targets and stabilizes cardiolipin in the inner mitochondrial membrane. Cardiolipin is essential for electron transport chain complex organization and efficiency. By stabilizing cardiolipin, SS-31 improves mitochondrial bioenergetics, reduces electron leak and ROS production, and prevents cytochrome c release (apoptosis).

Evidence Base

Multiple Phase II and III clinical trials conducted by Stealth BioTherapeutics. In the TAZPOWER trial for Barth syndrome, the randomized crossover phase missed its primary endpoints; improvements in 6-minute walk distance and symptoms emerged in the open-label extension. The Phase 3 MMPOWER-3 trial in primary mitochondrial myopathy (n=218) did not meet its primary endpoints. The Phase 2a EMBRACE STEMI trial did not reduce infarct size. FDA's 2025 accelerated approval for Barth syndrome rests on improved knee extensor strength, an intermediate endpoint.

Safety Considerations

Extensive clinical trial safety data across multiple Phase II/III studies. Generally well-tolerated. Injection site reactions are the most common adverse effect. FDA-approved labeling (Forzinity, 2025) now defines its safety profile in Barth syndrome. More safety data available than most peptides in this category.

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